Norwegian College of Fishery Science, Faculty of Biosciences, Fisheries & Economics, University of Tromsø - The Arctic University of Norway, Tromsø, Norway.
Department of Pathology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
Sci Rep. 2018 Feb 23;8(1):3565. doi: 10.1038/s41598-018-21895-9.
While TLR-activated pathways are key regulators of B cell responses in mammals, their impact on teleost B cells are scarcely addressed. Here, the potential of Atlantic salmon B cells to respond to TLR ligands was shown by demonstrating a constitutive expression of nucleic-acid sensing TLRs in magnetic sorted IgM cells. Of the two receptors recognizing CpG in teleosts, tlr9 was the dominating receptor with over ten-fold higher expression than tlr21. Upon CpG-stimulation, IgM secretion increased for head kidney (HK) and splenic IgM cells, while blood B cells were marginally affected. The results suggest that CpG directly affects salmon B cells to differentiate into antibody secreting cells (ASCs). IgM secretion was also detected in the non-treated controls, again with the highest levels in the HK derived population, signifying that persisting ASCs are present in this tissue. In all tissues, the IgM cells expressed high MHCII levels, suggesting antigen-presenting functions. Upon CpG-treatment the co-stimulatory molecules cd83 and cd40 were upregulated, while cd86 was down-regulated under the same conditions. Finally, ifna1 was upregulated upon CpG-stimulation in all tissues, while a restricted upregulation was evident for ifnb, proposing that salmon IgM B cells exhibit a type I IFN-response.
虽然 TLR 激活途径是哺乳动物 B 细胞反应的关键调节剂，但它们对硬骨鱼类 B 细胞的影响却鲜有报道。在这里，通过证明在磁性分选的 IgM 细胞中组成性表达核酸感应 TLR，显示了大西洋鲑鱼 B 细胞对 TLR 配体产生反应的潜力。在识别鱼类 CpG 的两种受体中，tlr9 是占主导地位的受体，其表达水平比 tlr21 高十倍以上。在 CpG 刺激后，头肾 (HK) 和脾 IgM 细胞的 IgM 分泌增加，而血液 B 细胞则受到轻微影响。结果表明 CpG 直接影响鲑鱼 B 细胞分化为分泌抗体的细胞 (ASC)。未经处理的对照组也检测到 IgM 分泌，同样以 HK 来源的群体水平最高，表明该组织中存在持续存在的 ASC。在所有组织中，IgM 细胞表达高水平的 MHCII，表明其具有抗原呈递功能。在 CpG 处理后，共刺激分子 cd83 和 cd40 上调，而在相同条件下 cd86 下调。最后，在所有组织中，ifna1 在 CpG 刺激后上调，而 ifnb 则受到限制上调，这表明鲑鱼 IgM B 细胞表现出 I 型 IFN 反应。
